Prevention of the in vitro myelosuppressive effects of glucocorticosteroids by interleukin 1 (IL 1).
We investigated the effects of dexamethasone on the formation of granulocyte/macrophage colonies by murine bone marrow cells cultured with colony-stimulatory factors (CSF) in semisolid agar. Dexamethasone (10(-7) M) completely inhibited the formation of colonies in response to L929 CSF but had no effect on the response to CSF in the culture supernatants of the murine macrophage cell line, PU5-1.8. We postulated that a cofactor, interleukin 1, present in the PU5-1.8 supernatants was responsible for protecting colony formation against steroid suppression. Interleukin 1, isolated from culture supernatants of PU5-1.8 and from culture supernatants of human acute monocytic leukemia cells, blocked the inhabitory effects of dexamethasone on colony formation in response to L929 CSF. Moreover, dexamethasone inhibited colony formation in response to PU5-1.8 culture supernatants when interleukin 1 was absent. We also examined interleukin 2 for possible protective effects. Although crude interleukin 2 preparations (supernatants of spleen cells cultured with concanavalin A) blocked dexamethasone inhibition, purified interleukin 2 had no protective effects. These data indicate that interleukin 1 protects colony formation by a pathway that is independent of interleukin 2 and that supernatants of spleen cells activated with concanavalin A probably contain significant amount of interleukin 1.
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D006098:Granulocytes / Q000166:cytology; D006801:Humans; D007375:Interleukin-1; D007376:Interleukin-2 / Q000627:therapeutic use; D008264:Macrophages / Q000166:cytology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011506:Proteins / Q000627:therapeutic use*
D003115:Colony-Stimulating Factors; D007375:Interleukin-1; D007376:Interleukin-2; D011506:Proteins; D003907:Dexamethasone